South Africa (SA) has the largest number of people living with HIV/AIDS (PLWHA) in the world. Youth in SA are experiencing the fastest increase in new HIV infections, and in the Western Cape region, new infections are increasingly fueled by mental health problems and substance use. Families can be effective collaborators in HIV prevention efforts, but no family-based interventions exist for South African teens, particularly those with mental health problems and drug/alcohol use. This developmental study will adapt and pilot test a multi-level, highly promising, HIV and alcohol/drug use prevention program (Project STYLE) for South African caregivers and their teens receiving outpatient mental health services. Project STYLE was designed and tested with 750 mentally ill teens across three US cities, and we will systematically adapt it for the South African context using a combination of ADAPT-ITT and CDC guidelines. Stage 1 will involve extensive formative work (e.g., focus groups, feedback groups, in-depth interviews, theater testing), revisions to survey instruments and the curriculum, and translation/back-translation into Afrikaans and isiXhosa. We will assemble a CAB to advise in the adaptations and revisions. In Stage 2, we will pilot test the revised intervention with two groups of 14 - 18 year old parent-teen dyads receiving mental health services. Teens will be male and female from all ethnic groups (i.e., White, Black, and Colored). We will revise study procedures and materials based on comprehensive participant evaluations, observations, and facilitator ratings. In Stage 3, we will re-test the revised program with 60 parent-teen dyads randomly assigned to Project STYLE versus a control group. All participants will complete baseline and 3-month follow-up interviews to evaluate tracking, retention, and preliminary treatment effects. Guided by a Social-Personal framework6 of HIV-risk and the Theory of Gender and Power, the intervention will target personal attributes, peer and partner relationship processes, and family context to reduce risky sexual behavior and drug/alcohol use among South African youth. Given the exploratory nature of the study, we will cautiously examine change in theoretical mediators and risky sexual behavior and substance abuse as a function of program participation, and we will determine the pretest-posttest effect size of program impact on HIV-risk behavior between groups. The long-term goal of the study is to adapt a highly promising and scientifically-based HIV and substance use prevention program for South African teens and parents that can be tested in a large-scale effectiveness study. This study is consistent with R34 guidelines to support the early phase of intervention development and preliminary testing to examine feasibility, acceptability, and tolerability. PUBLIC HEALTH RELEVANCE: Sub-Saharan Africa is the global epicenter of the AIDS epidemic, and South Africa is estimated to have the largest number of people living with HIV/AIDS in the world. With youth experiencing the fastest increase in new HIV infections in South Africa, stemming transmissions is a global public health priority. Unfortunately, national efforts have been disappointing; 50% of South African youth are sexually experienced, 25% were previously diagnosed with an STI, and 40% report sexual activity involving blood. Similarly, adolescent rates of alcohol and other drug use are rising, and age at first use (13 - 16 years old) for the majority (54%) is young. Likewise, despite high-risk taking among teens in psychiatric care, and the World Health Organization's statement that there can be no health without mental health, mental health has been a low priority in South Africa. Disproportionate rates of HIV infection among South Africans may reflect, in part, few available mental health services, while improved mental health care may reduce the spread of HIV/AIDS. In the Western Cape region of South Africa, associations among sexual risk taking, alcohol and drug use, and mental illness are fueling HIV/AIDS infections among youth. Families can be effective collaborators in HIV prevention efforts, but no family-based interventions exist for South African teens, particularly those with mental health problems and drug/alcohol use. This developmental study will adapt and pilot test a multi-level, highly promising, HIV and alcohol/drug use prevention program (Project STYLE) for this exceptionally high-risk population. Simultaneously addressing sexual risk taking, mental health, and substance use among South African youth has the potential to reduce these intersecting epidemics. The long-term goal of the proposed project is to develop an empirically-validated, theoretically-based family-focused HIV and substance use prevention program to reduce health risk behavior among South African youth with mental health problems.